The emergence and diversification of cell types is a leading factor in animal evolution. So far, systematic characterization of the gene regulatory programs associated with cell type specificity was limited to few cell types and few species. Here, we perform whole-organism single-cell transcriptomics to map adult and larval cell types in the cnidarian Nematostella vectensis, a non-bilaterian animal with complex tissue-level body-plan organization. We uncover eight broad cell classes in Nematostella, including neurons, cnidocytes, and digestive cells. Each class comprises different subtypes defined by the expression of multiple specific markers. In particular, we characterize a surprisingly diverse repertoire of neurons, which comparative analysis suggests are the result of lineage-specific diversification. By integrating transcription factor expression, chromatin profiling, and sequence motif analysis, we identify the regulatory codes that underlie Nematostella cell-specific expression. Our study reveals cnidarian cell type complexity and provides insights into the evolution of animal cell-specific genomic regulation.

Regulation of IL-2–producing CD4+ T cell numbers is controlled by a quorum-sensing feedback loop as regulatory T cells sense the IL-2 produced.

Heat-killed Brucella abortus (HBa) has been proposed as a carrier for therapeutic vaccines for individuals with immunodeficiency, due to its abilities to induce interleukin-2 (IL-2) and gamma interferon (IFN-␥) in both CD4؉ and CD8 ؉ T cells and to upregulate antigen-presenting cell functions (including IL-12 production). In the current study, we investigated the ability of HBa or lipopolysaccharide isolated from HBa (LPS-Ba) to elicit ␤-chemokines, known to bind to the human immunodeficiency virus type 1 (HIV-1) coreceptor CCR5 and to block viral cell entry. It was found that human peripheral blood mononuclear cells secreted ␤-chemokines following stimulation with HBa, and this effect could not be blocked by anti-IFN-␥ neutralizing antibodies. Among purified T cells, macrophage inflammatory protein 1␣ and 1␤ (MIP-1␣ and MIP-1␤, respectively) secretion was observed primarily in human CD8؉ T cells. The kinetics of ␤-chemokine induction in T cells were slow (3 to 4 days). The majority of ␤-chemokine-producing CD8 ؉ T cells also produced IFN-␥ following HBa stimulation, as determined by triple-color intracellular staining. A significant number of CD8 ؉ T cells contained stored MIP-1␤ that was released after HBa stimulation. Both HBa and LPS-Ba stimulated high levels of MIP-1␣ and MIP-1␤ production in elutriated monocytes and even higher levels in macrophages. In these cells, ␤-chemokine mRNA was upregulated within 30 min and proteins were secreted within 4 h of stimulation. The monocyte-and macrophage-derived ␤-chemokines were sufficient to block CCR5-dependent HIV-1 envelope-mediated cell fusion. These data suggest that, in addition to the ability of HBa to elicit antigen-specific humoral and cellular immune responses, HBa-conjugated HIV-1 proteins or peptides would also generate innate chemokines with antiviral activity that could limit local viral spread during vaccination in vivo.The discovery that several ␤-chemokines (i.e., macrophage inflammatory proteins 1␣ and 1␤ [MIP-1␣ and MIP-1␤, respectively] and RANTES) secreted by short-term human CD8 ϩ cell lines can effectively block infection of human peripheral blood mononuclear cells (PBMCs) with macrophage-